The disease burden of the more than 80 distinct autoimmune diseases in the United States is enormous, collectively affecting 14 to 22 million people, an estimated 5-8% of the U.S. population.
Immunosuppression is the therapy of choice for most autoimmune diseases. Conventional agents that induce non-specific immunosuppression, such as non-steroidal anti-inflammatory drugs, glucocorticoids, and methotrexate have traditionally been the mainstay of therapy for many autoimmune diseases. While helpful, these medications are not always fully efficacious and are associated with significant toxicity when used chronically. Additionally, by non-specifically suppressing the immune system, these medications substantially increase patient susceptibility to infections.
Over the past few years, a number of new medications have become available which are able to specifically target certain arms of the immune response. While such approaches clearly represent a step forward in focusing immunosuppressive therapy, none does so in an antigen-specific manner. Consequently, these new medications still increase patient susceptibility to infections, albeit to a smaller range of organisms than non-specific immunosuppressive agents. This phenomenon is exemplified by the recent findings that tumor necrosis factor inhibitors, despite blocking the activity of only one cytokine, increase the risk of pneumonia, severe skin infections, and reactivation of prior tuberculosis.
Given the increased risk to infection that occurs when even specific facets of the immune system are inhibited, an alternative therapy for autoimmune diseases would be one that suppresses only self-reactive immune responses. Such a therapy would, ideally, be efficacious without compromising the body's ability to fight off infections. Several autoimmune diseases appear to be caused in large part by Th1-driven inflammation. Examples include type 1 diabetes, multiple sclerosis, Crohn's disease, inflammatory bowel disease, rheumatoid arthritis, and posterior uveitis. While the Th1/Th2 paradigm has evolved somewhat since its first description in 1986, it is still generally accepted that Th1 and Th2 responses have the ability to counter regulate each other. In particular, IL-4 suppresses differentiation of naïve T-cells into Th1 cells, resulting in decreased Th1 cytokine production and decreased Th1 cell proliferation in response to Th1-inducing antigens. Thus, there is a need for new treatment modalities that selectively down regulate Th1 responses.